Why are PARP Inhibitors Effective in Cancer Therapy?
PARP inhibitors exploit a concept known as "synthetic lethality," where two genetic events, each of which is non-lethal on its own, become lethal when occurring together. Cancer cells with BRCA mutations are already compromised in their ability to repair double-strand DNA breaks through homologous recombination. When PARP is inhibited, these cells cannot efficiently repair single-strand breaks, leading to double-strand breaks during DNA replication. This overwhelming DNA damage causes the cancer cells to die, while normal cells remain relatively unaffected.
